Menarini Reports Positive Phase 3 Results for Obicetrapib in Treating Familial Hypercholesterolemia

The Menarini Group has announced promising results from the Phase 3 BROOKLYN clinical trial, sponsored by NewAmsterdam Pharma Company N.V. The trial focused on evaluating the efficacy of obicetrapib in adult patients with heterozygous familial hypercholesterolemia (HeFH) whose low-density lipoprotein cholesterol (LDL-C) levels were not adequately controlled despite being on maximally tolerated lipid-lowering therapies.

The BROOKLYN trial successfully met its primary endpoint by achieving a mean LDL-C reduction of 36.3% compared to placebo at week 12, which was sustained at 41.5% at 52 weeks. Additionally, more than half of the patients reached LDL-C levels below 70 mg/dl. The reductions in other biomarkers, such as non-HDL-C, ApoB, and Lp(a), were also statistically significant and aligned with results from previous studies.

Obicetrapib demonstrated a favorable safety profile in the trial, with no increase in blood pressure. Treatment-related adverse events occurred in 6.8% of patients in the placebo group compared to 4.3% in the obicetrapib group. No serious adverse events related to the study drug were reported in either group, and the treatment discontinuation rate was lower for obicetrapib (7.6%) compared to placebo (14.4%).

Stephen Nicholls, the principal investigator of the obicetrapib development program, expressed optimism about obicetrapib's potential as a high-efficacy, oral treatment option for patients with HeFH who are already on multiple lipid-lowering therapies. Katherine Wilemon, Founder and CEO of the Family Heart Foundation, highlighted the significant unmet needs in this patient population, emphasizing the importance of achieving guideline-recommended LDL-C levels to reduce the risk of major adverse cardiovascular events.

Elcin Barker Ergun, Chief Executive Officer of the Menarini Group, underscored the global burden of cardiovascular diseases (CVDs) and the need for additional treatment options. He noted that obicetrapib's ability to significantly reduce LDL-C over a year represents a critical milestone in their mission to combat cardiovascular diseases, especially for patients with HeFH in Europe.

The Phase 3 BROOKLYN trial was a 52-week, global, randomized, double-blind, placebo-controlled study. It evaluated the efficacy and safety of 10 mg obicetrapib as an adjunct to maximally tolerated lipid-lowering therapies in patients with HeFH. Conducted across multiple sites in North America, Europe, and Africa, the trial included 354 patients randomized in a 2:1 ratio to receive either obicetrapib or placebo once daily. The mean baseline LDL-C in the obicetrapib group was 123 mg/dL, despite high-intensity statin use by approximately 79% of patients.

The primary objective was to assess the impact of obicetrapib on LDL-C levels, with secondary objectives including its effects on non-HDL-C, ApoB, and lipoprotein (a). The trial also aimed to evaluate the safety and tolerability of obicetrapib.

Obicetrapib is part of a broader Phase 3 clinical development program that includes four studies involving over 12,250 patients. These studies aim to further evaluate obicetrapib as a monotherapy and as part of a fixed-dose combination with ezetimibe. The program includes trials such as BROADWAY, which focuses on patients with established ASCVD and/or HeFH, TANDEM, which investigates the combination of obicetrapib and ezetimibe, and PREVAIL, a cardiovascular outcomes trial.

Obicetrapib is a novel, low-dose CETP inhibitor designed to overcome the limitations of existing LDL-lowering treatments. Previous Phase 2 trials have shown that obicetrapib effectively lowers LDL-C with good tolerability. The ongoing Phase 3 trials aim to provide additional evidence of its efficacy and safety for patients with cardiovascular disease.